This project emphasizes the mechanisms of aging related to connective tissue, bone, carbohydrate and lipid metabolism with the multifactorial diseases of atherosclerosis, diabetes mellitus and osteoporosis. Particular focus is on the cellular mechanisms of aging using cultured cells as experimental models. Studies use human fibroblasts and thus the metabolism of cultured cells forms both a conceptual and technological framework for a large portion of the project and provides a meaningful basis for interaction and collaboration among the investigators. Individual project will focus on: 1) Factors controlling the transport of cholesterol rich and triglyceride-rich lipoproteins in plasma and into the arterial wall in relation to aging and atherogenesis; 2) The regulation of hormone secretion in relation to aging; 3) The synthetic activities and metabolic responses of connective tissue cells in relation to aging, particularly protein synthesis by human fibroblasts and reactions to osteoclsts in relation to the pathogenesis of osteoporosis.